Fatty Acid Composition of Low-Density Lipoprotein Influences Its Susceptibility to Autoxidation

Abstract

Low-density lipoprotein (LDL) oxidation was studied using copper or the water-soluble initiator azobis(2-amidinopropane) dihydrochloride (ABAP) to catalyze the reaction. These studies were carried out with purified, native LDLs that had a well-defined composition and which contained different concentrations of polyunsaturated fatty acids (PUFA) and alpha-tocopherol. The LDL was obtained from nonhuman primates fed diets enriched in cholesterol and one of four types of fatty acids: saturated (Sat), monounsaturated (Mono), omega-6 (omega-6FA), or omega-3 (omega-3FA) fatty acids. The PUFA concentration of the LDLs depended upon the diet and had the following order: omega-6FA > Sat approximately Mono approximately omega-3FA. Linoleic acid was the predominant PUFA in all of the LDLs. The rates of oxidation were linearly dependent upon the concentration of PUFA. When ABAP was used to initiate oxidation the lag time was linearly related to the amount of alpha-tocopherol. However, with copper catalysis no linear correlation was evident. If the different enrichments were analyzed independently, it was found that copper-catalyzed oxidation of LDLs enriched with omega-6 and omega-3 fatty acids showed a linear correlation between the lag time and the amount of alpha-tocopherol but that LDLs enriched with Sat or Mono fatty acids did not show a correlation. These results demonstrate that the rate of oxidation is dependent upon PUFA concentration and that the ability of alpha-tocopherol to inhibit oxidation depends upon the lipid environment and the mode of initiation.